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Structural analysis of an anti-estradiol antibody

Lamminmaki, U; Villoutreix, BO; Jauria, P; Saviranta, P; Vihinen, Mauno LU ; Nilsson, L; Teleman, O and Lovgren, T (1997) In Molecular Immunology 34(16-17). p.1215-1226
Abstract
An anti-estradiol antibody with improved specificity is searched for by combining steroid analog binding studies, mutant antibodies obtained from a phage-display library and structural modeling. Three-dimensional models for the anti-estradiol antibody 57-2 were constructed by comparative model building. Estradiol and analogs were docked into the combining site and molecular dynamics simulation was used to further refine this area of the protein. Cross-reactivities measured against 36 steroid analogs were used to help in the docking process and to evaluate the models. The roles of a number of residues were assessed by characterization of cross-reactivity mutants obtained from a phage display library. The cross-reactivity data and the... (More)
An anti-estradiol antibody with improved specificity is searched for by combining steroid analog binding studies, mutant antibodies obtained from a phage-display library and structural modeling. Three-dimensional models for the anti-estradiol antibody 57-2 were constructed by comparative model building. Estradiol and analogs were docked into the combining site and molecular dynamics simulation was used to further refine this area of the protein. Cross-reactivities measured against 36 steroid analogs were used to help in the docking process and to evaluate the models. The roles of a number of residues were assessed by characterization of cross-reactivity mutants obtained from a phage display library. The cross-reactivity data and the results observed for mutants are explained by the structural model, in which the estradiol D-ring inserts deeply into the binding site and interacts with the antibody through at least one specific hydrogen bond. The binding data strongly suggest that this hydrogen bond connects the estradiol 17-hydroxyl group with the side chain of Gin H35. As expected for the binding of a small aromatic molecule, the antibody binding site contains many aromatic residues, e.g. Trp H50, H95 and L96 and Tyr L32, L49 and Phe L91. (C) 1997 Published by Elsevier Science Ltd. All rights reserved. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
protein modeling, antibody, steroid, estradiol, cross-reactivity, protein engineering, antibody-antigen interactions
in
Molecular Immunology
volume
34
issue
16-17
pages
1215 - 1226
publisher
Pergamon
external identifiers
  • wos:000072787000011
  • scopus:0344701071
ISSN
1872-9142
DOI
10.1016/S0161-5890(97)00085-0
language
English
LU publication?
no
id
23236916-85c4-4e0b-b813-d59527c50376 (old id 3852770)
date added to LUP
2013-06-28 14:31:26
date last changed
2017-01-01 06:37:20
@article{23236916-85c4-4e0b-b813-d59527c50376,
  abstract     = {An anti-estradiol antibody with improved specificity is searched for by combining steroid analog binding studies, mutant antibodies obtained from a phage-display library and structural modeling. Three-dimensional models for the anti-estradiol antibody 57-2 were constructed by comparative model building. Estradiol and analogs were docked into the combining site and molecular dynamics simulation was used to further refine this area of the protein. Cross-reactivities measured against 36 steroid analogs were used to help in the docking process and to evaluate the models. The roles of a number of residues were assessed by characterization of cross-reactivity mutants obtained from a phage display library. The cross-reactivity data and the results observed for mutants are explained by the structural model, in which the estradiol D-ring inserts deeply into the binding site and interacts with the antibody through at least one specific hydrogen bond. The binding data strongly suggest that this hydrogen bond connects the estradiol 17-hydroxyl group with the side chain of Gin H35. As expected for the binding of a small aromatic molecule, the antibody binding site contains many aromatic residues, e.g. Trp H50, H95 and L96 and Tyr L32, L49 and Phe L91. (C) 1997 Published by Elsevier Science Ltd. All rights reserved.},
  author       = {Lamminmaki, U and Villoutreix, BO and Jauria, P and Saviranta, P and Vihinen, Mauno and Nilsson, L and Teleman, O and Lovgren, T},
  issn         = {1872-9142},
  keyword      = {protein modeling,antibody,steroid,estradiol,cross-reactivity,protein engineering,antibody-antigen interactions},
  language     = {eng},
  number       = {16-17},
  pages        = {1215--1226},
  publisher    = {Pergamon},
  series       = {Molecular Immunology},
  title        = {Structural analysis of an anti-estradiol antibody},
  url          = {http://dx.doi.org/10.1016/S0161-5890(97)00085-0},
  volume       = {34},
  year         = {1997},
}